1. Field of the Invention
The present invention relates generally to the fields of medicine and microbiology. More particularly, it concerns methods of reducing microbial organisms from indwelling medical devices, medical equipment and other surfaces.
2. Description of Related Art
Medical devices, such as vascular catheters, have improved the quality of medical care. However, infections resulting from the colonization of organisms embedded in biofilm are the most frequent complication associated with the use of these and other indwelling and/or prosthetic devices. In fact, infections are the most serious complications associated with indwelling central venous catheters (CVCs) (Maki et al., 1998). It is estimated that more than 200,000 catheter-related bloodstream infections (CRBSI) occur annually in the United States alone (Kluger et al., 1999). Staphylococcus epidermidis, Staphylococcus aureus and Candida species are the leading organisms causing CRBSI (Maki et al., 1998; Raad et al., 2002).
Because intralumenal colonization is the major source for the migration of organisms leading to bloodstream infections in long-term silicone catheters (Raad et al., 1993), recent guidelines by the CDC and Infectious Diseases Society of America have proposed the use of intralumenal antimicrobial lock solutions for the prevention and treatment of CRBSI (Mermel et al., 2001; Centers for Disease Control and Prevention, 2002). Most long-term CVCs are typically flushed with heparin. An antimicrobial/anticoagulant combination consisting of vancomycin/heparin with and without ciprofloxacin was shown to reduce the risk of catheter-related bacteremia caused by gram-positive organisms (Carratala et al., 1999; Henrickson et al., 2002; Schwartz et al., 1990). However, with the rise of incidences of infection by vancomycin resistant gram-positive bacteria, concerns have been raised over the use of vancomycin flush solutions and their potential for increasing the risk of vancomycin resistance (Spafford et al., 1994).
Recently the present inventor demonstrated that a flush solution comprising minocycline and EDTA (M-EDTA) is highly efficacious in preventing catheter-related colonization, bacteremia and endocarditis in rabbits (Raad et al., 2002). When compared to a heparin flush solution, M-EDTA was found to decrease the risk of catheter-related colonization and infection in hemodialysis patients as well as pediatric cancer patients (Bleyer et al., 2000; Chatzinikolaou et al., 2002). EDTA has an equivalent anticoagulant activity to heparin (Reardon et al., 1991). An anticoagulant in flush solutions is necessary to prevent the thrombotic occlusion of the catheter lumen.
Although M-EDTA has been found to be efficacious in preventing CRBSI, this solution may not be applicable given some of the limitations of the real world of clinical practice. In the animal and clinical studies, the M-EDTA lock solution was required to be exposed to the surface of the indwelling medical device, such as the lumen of catheters, for at least 4 hours. In vitro studies have also shown that M-EDTA requires at least 4 hours of dwell time to eradicate organisms that colonize the lumen of the catheter (see in particular data in U.S. Pat. No. 5,362,754, columns 11 and 12, and Tables 3, 4 and 5 as well as in U.S. Pat. No. 5,688,516, columns 15 and 16, and Tables 3, 4, and 5). Providing a four hour exposure time to reduce microbes using the M-EDTA solution is usually not possible in critically ill patients who require continuous infusion therapy, including parenteral nutrition.
Thus, there is an acute need in the art to develop compositions and methods for rapid reduction and/or eradication of microbes from indwelling medical devices without interruption of the use of the device in patients for too long a period. In addition, there is also a need for better and improved antimicrobial compositions.